P. Sytze van Dam

Effects of Growth Hormone Substitution Therapy on Cognitive Functioning in Growth Hormone Deficient Patients: A Functional MRI Study

Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such patients. Thirteen childhood-onset GHD patients (mean age 27.3 ± 6.9 years) were included in a double-blind, placebo-controlled study. The effects of 6 months of GH replacement or placebo therapy were studied using neuropsychological tests and fMRI. One patient was excluded from the study due to noncompliance with the protocol. Six months of GH substitution in these GHD patients resulted in improved memory functioning, both for long-term and working memory. fMRI showed activations during the working memory task in prefrontal, parietal, motor, and occipital cortices, as well as in the right thalamus and anterior cingulate cortex. Decreased activation in the ventrolateral prefrontal cortex was observed after GH treatment as compared with placebo treatment, indicating decreased effort and more efficient recruitment of the neural system involved. It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex. GH substitution in GHD patients is beneficial for cognitive functioning, the effects of which can be visualized by means of neuroimaging.

Childhood-onset growth hormone deficiency, cognitive function and brain N-acetylaspartate

Cognitive deficits have been reported in adults with childhood-onset growth hormone (GH) deficiency. We evaluated cognitive deficits simultaneously with parameters for neuronal integrity using (1)H magnetic resonance spectroscopy (MRS) in a cross-sectional design. We studied 11 adults (mean age 24.5 years) with childhood-onset GH deficiency, which persisted after reaching final height. All subjects were evaluated after interruption of GH supplementation for at least 3 months. We performed neuropsychological assessment (NPA) using tests evaluating memory, mental processing speed, reading ability and executive functioning. MRS was used to assess brain N-acetylaspartate (NAA)/choline ratios. Data were compared with an age-, sex- and education-matched control group (n=9, mean age 27.3 years). NPA demonstrated attenuated performance of the patients in the delayed verbal memory recall score (P<0.05) and the trail making A test (P<0.05), a measure of planning of behavior, processing speed and attention. Other neuropsychological tests were not affected. NAA/choline ratios were significantly reduced (P<0.01) in GH deficient subjects. Specific cognitive defects indicating affected memory and attention were found in patients with childhood-onset GH deficiency. These defects occur simultaneously with reduced neuronal integrity.

Effect of obesity and morbid obesity on the growth hormone (GH) secretion elicited by the combined GHRH + GHRP-6 test

Objectiveu2002 Obesity is characterized by low basal levels of growth hormone (GH) and impeded GH release. However, the main problem arises in the diagnosis of GH deficiency in adults, as all accepted cut‐offs in the diagnostic tests of GH reserve are no longer valid in obese subjects. In this work, the role of obesity in the GH response elicited by the GHRH + GHRP‐6 test was assessed in a large population of obese and nonobese subjects.

Growth Hormone Deficiency and Memory Functioning in Adults Visualized by Functional Magnetic Resonance Imaging

Cognitive functioning, especially memory performance, is known to be impaired in patients with childhood-onset growth hormone deficiency (CO-GHD), and growth hormone substitution has been found to counteract this memory impairment. Neuropsychological and functional magnetic resonance imagining (fMRI) data acquired during a working memory task in 13 childhood-onset GH-deficient patients were compared with 13 age, sex and education level matched healthy controls. Results demonstrated that there is no difference in the quality of the performance in the working memory task between GH-deficient patients and control subjects. However, memory speed was found to be subnormal in patients. Concerning mood, patients reported more complaints of fatigue, and less vigor. Imaging data showed that patients had increased activity in dorsolateral/ventrolateral prefrontal cortex, anterior cingulate cortex, parietal cortex, supplementary motor and motor cortex, as well as in the thalamus and precuneus area. Increasing task load was also associated with an increase in brain activity in similar areas in patients compared to control subjects. In conclusion, this fMRI study shows that GH-deficient patients have a subnormal memory speed, but no impaired quality of memory performance, which may be due to compensatory recruitment of dorsal prefrontal brain regions. These findings indicate that the GH-IGF-1 axis contributes to prefrontal functioning in patients with CO-GHD.

Growth hormone and selective attention: A review

INTRODUCTIONnThe relation between growth hormone (GH) secretion and general cognitive function has been established. General cognitive functioning depends on core functions including selective attention, which have not been addressed specifically in relation to GH. The present review addresses current insights about specific effects of growth hormone deficiency (GHD) on varieties of selective attention, as well as effects of GH suppletion.nnnMATERIALS AND METHODSnStudies investigating relationships between GH status and valid measures of selective or divided attention were reviewed.nnnRESULTS AND DISCUSSIONnThere are no indications that GHD is characterized by impaired attribute selection, interference control, or attentional switching. In contrast, a few studies point to a deficit in integrated processing of multiple dimensions, as well as speed of information processing. There is also weak evidence for beneficial effects of GH replacement in the opposite direction in these domains.nnnCONCLUSIONSnThe function of integrated processing of multiple stimulus dimensions may be based on neural mechanisms in the anterior cingulate cortex and its extensive connections to the hippocampus, the latter being known to be rich in GH receptors.

3rd Annual ENETS Conference

s C1–C61 29

Diagnosis of growth hormone deficiency after pituitary surgery: the combined acipimox/GH‐releasing hormone test

objective Reduction of plasma free fatty acids leads to enhanced GH response after stimulation by GH‐releasing hormone (GHRH). We studied the clinical usefulness of combined administration of acipimox and GHRH for the diagnosis of GH deficiency.